Method for the production of poly(methyl methacrylate) (PMMA) membranes and uses thereof

Abstract

A poly(methyl methacrylate) (PMMA) membrane having a highly porous, reticulated, 3-D structure suitable for lateral flow diagnostic applications is described. Also described is a method for producing a poly(methyl methacrylate) (PMMA) membrane that comprises the steps of mixing a suitable amount of PMMA, a solvent and a optionally one of either a co-solvent or a non-solvent to produce a solution, casting a thin film of the solution onto a support, and removal of the solvent from the solution to produce the PMMA membrane. A lateral flow diagnostic device comprising a highly porous PMMA membrane as a reaction membrane is also described.

The invention claimed is: 
     
       1. A method for producing a homogenous and symmetric poly(methyl methacrylate) (PMMA) membrane on a solid support material, the method comprising the steps of:
 (i) mixing a suitable amount of PMMA, a solvent, and a C 2 -C 6  co-solvent to produce a PMMA solution with increased sensitivity to temperature fluctuations, wherein the C 2 -C 6  co-solvent functions as a solvent above a certain temperature and as a non-solvent below said certain temperature; 
 (ii) casting a thin film of the PMMA solution onto a solid support material; and 
 (iii) affecting the temperature of the cast PMMA solution on the solid support material so that the cast PMMA solution becomes unstable and separates out into two phases, wherein the C 2 -C 6  co-solvent transitions from a co-solvent in the solution to a non-solvent, thereby producing the homogenous and symmetric PMMA membrane on the solid support material. 
 
     
     
       2. The method according to  claim 1 , in which the PMMA solution is heated to a temperature above an upper critical solution temperature of the solution in step (i), the PMMA membrane is then TIPS-cast in step (ii), wherein the cast solution is cooled by casting onto a surface below its upper critical solution temperature followed by removal of the solvent/co-solvent. 
     
     
       3. The method according to  claim 1 , in which the PMMA membrane is VIPS-cast in step (ii), wherein solvent and co solvents is removed from the PMMA solution in a sequential manner by evaporation that is controlled by air flow over the PMMA solution. 
     
     
       4. The method according to  claim 1 , in which the PMMA membrane is LIPS-cast in step (ii) and the thin film of the PMMA solution is immersed into a coagulation bath containing a non-solvent and optionally a solvent, whereby exchange of solvent and non-solvent results in the formation of a symmetric porous PMMA membrane on a solid support material and avoids skin layer formation; wherein the non-solvent is selected from the group consisting of ethyl ether, water, glycerol, ethylene glycol, methanol and ethanol, or a combination thereof. 
     
     
       5. The method according to  claim 1 , in which the PMMA membrane is hybrid-cast in step (ii), the solvent and co-solvent are removed from the PMMA solution by evaporation that is controlled by air flow over the PMMA membrane, and the PMMA membrane is then immersed into a coagulation bath containing a non-solvent whereby the final PMMA membrane structure is fixed. 
     
     
       6. The method according to  claim 1 , in which the PMMA membrane is temperature- and evaporation-cast, wherein the PMMA solution is heated to a temperature above an upper critical solution temperature of the solution in step (i); the PMMA membrane is then TVIPS-cast in step (ii), wherein the PMMA solution is cooled by casting onto a surface below its upper critical solution temperature, and wherein solvent and co-solvent are removed from the cast solution in a sequential manner by evaporation that is controlled by air flow over the film. 
     
     
       7. The method according to  claim 1 , in which the support is cooled such that a temperature difference of 10° C. exists between the support temperature and the upper critical solution temperature of the PMMA solution. 
     
     
       8. The method according to  claim 1 , in which the solution comprises 2-14 wt % PMMA and 55-96 wt % solvent/co-solvent. 
     
     
       9. The method according to  claim 1 , wherein the solvent is selected from the group consisting of dichloroethane, acetic acid, acetone, iso-propanol, n-propanol, n-butanol, chloroform, toluene, 1,4 dioxane, tetrahydrofuran, ethyl acetate, methyl ethyl ketone or a combination thereof. 
     
     
       10. The method according to  claim 1 , wherein the C 2 -C 6  co-solvent is an alcohol selected from the group consisting of n-propanol, iso-propanol, 1-butanol, 2-butanol, tert-butanol, 2-methylbutan-2-ol, 3-methylbutan-2-ol, 2,2-dimethylpropan-1-ol, pentan-3-ol, pentan-2-ol, pentan-1-ol, 1-hexanol, 2-hexanol, 3-hexanol, 2-methyl-2-pentanol, 2,3-dimethyl-2-butanol, 3-methyl-3-pentanol and cyclo-hexanol. 
     
     
       11. The method according to  claim 10 , in which the PMMA membrane on the solid support material is rendered hydrophilic by treatment with any one of the following: hydrolysis, aminolysis, silanisation, aqueous solutions of surfactants, ultraviolet radiation, plasma treatment, electron beam radiation and ozonation, or combinations thereof while maintaining the ability to bind proteins via hydrophobic interactions. 
     
     
       12. A porous homogeneous and symmetric poly(methyl methacrylate) (PMMA) membrane on a solid support material produced by a method comprising the steps of:
 (i) mixing a suitable amount of PMMA, a solvent, and a C 2 -C 6  co-solvent to produce a PMMA solution with increased sensitivity to temperature fluctuations, wherein the C 2 -C 6  co-solvent functions as a solvent above a certain temperature and as a non-solvent below said certain temperature; 
 (ii) casting a thin film of the PMMA solution onto a solid support material; and 
 (iii) affecting the temperature of the cast PMMA solution on the solid support material so that the cast PMMA solution becomes unstable and separates out into two phases, and wherein the C2-C6 co-solvent transitions from a co-solvent in the solution to a non-solvent, thereby producing the homogenous and symmetric PMMA membrane on the solid support material. 
 
     
     
       13. The porous symmetric poly(methyl methacrylate) (PMMA) membrane on a solid support material according to  claim 12  having a symmetric reticulated 3-D matrix structure and a porosity of at least 85%, as determined by weight volume calculations. 
     
     
       14. The porous symmetric poly(methyl methacrylate) (PMMA) membrane on a solid support material according to  claim 12 , wherein the membrane has an average pore size of 0.5-30 m. 
     
     
       15. A lateral flow diagnostic device comprising a reaction membrane, characterized in that the reaction membrane comprises a symmetric porous poly(methyl methacrylate) (PMMA) membrane and solid support composite according to  claim 12 . 
     
     
       16. A device for performing an immunoassay that comprises a homogenous and symmetric poly(methyl methacrylate) membrane on a solid support produced by a method comprising the steps of:
 (i) mixing a suitable amount of PMMA, a solvent, and a C 2 -C 6  co-solvent to produce a PMMA solution with increased sensitivity to temperature fluctuations, wherein the C 2 -C 6  co-solvent functions as a solvent above a certain temperature and as a non-solvent below said certain temperature; 
 (ii) casting a thin film of the PMMA solution onto a solid support material; and 
 (iii) affecting the temperature of the cast PMMA solution on the solid support material so that the cast PMMA solution becomes unstable and separates out into two phases, and wherein the C2-C6 co-solvent transitions from a co-solvent in the solution to a non-solvent, thereby producing the homogenous and symmetric PMMA membrane on the solid support material.